A perspective on pathogenesis of post-COVID syndrome

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Аннотация

In 2023, the World Health Organization declared the COVID-19 pandemic caused by SARS-CoV-2 officially over. The infection has now transitioned into seasonal respiratory viral infections. However, one of the major health concerns persisting beyond the pandemic is post-COVID syndrome — a condition characterized by the persistence of COVID-19 symptoms or the emergence of new symptoms three months after the initial illness. The common mechanisms underlying post-COVID syndrome include immune dysregulation, viral persistence, chronic systemic inflammation, autoimmune manifestations, thrombosis, vascular endothelial dysfunction, myocarditis, myocardial infarction, ischemic heart disease, and pulmonary fibrosis. A significant autoimmune feature of post-COVID syndrome is the high prevalence of autoantibodies, including those targeting interferons, which can neutralize the biological activity of these protective cytokines. The combined effects of these mechanisms lead to a wide range of complications affecting multiple organ systems, including neurological and neuropsychiatric disorders. The exact pathophysiological mechanisms of post-COVID syndrome and their causal relationships remain to be fully understood. This is necessary to build on accumulated experience, be fully prepared for future infectious challenges, and prevent further casualties. This review examines the clinical manifestations and pathogenesis of post-COVID syndrome.

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Авторлар туралы

Nikolay Klimov

Institute of Experimental Medicine

Email: nklimov@mail.ru
ORCID iD: 0000-0002-5243-8085
SPIN-код: 6093-7430

MD, Cand. Sci. (Medicine)

Ресей, Saint Petersburg

Andrey Simbirtsev

Institute of Experimental Medicine; State Research Institute of Highly Pure Biopreparations

Хат алмасуға жауапты Автор.
Email: simbas@mail.ru
ORCID iD: 0000-0002-8228-4240
SPIN-код: 2064-7584

MD, Dr. Sci. (Medicine), Professor, Corresponding Member of the Russian Academy of Sciences

Ресей, Saint Petersburg; Saint Petersburg

Әдебиет тізімі

  1. Biancolella M, Colona VL, Luzzatto L, et al. COVID-19 annual update: a narrative review. Hum Genomics. 2023;17(1):68. doi: 10.1186/s40246-023-00515-2
  2. Zhu J, Zhong Z, Ji P, et al. Clinicopathological characteristics of 8697 patients with COVID-19 in China: a meta-analysis. Fam Med Community Health. 2020;8(2):e000406. doi: 10.1136/fmch-2020-000406 Erratum in: Fam Med Community Health. 2020;8(2):e000406corr1. doi: 10.1136/fmch-2020-000406corr1
  3. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–422. doi: 10.1016/S2213-2600(20)30076-X Erratum in: Lancet Respir Med. 202;8(4):e26. doi: 10.1016/S2213-2600(20)30085-0
  4. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5 Erratum in: Lancet. 2020;395(10223):496. doi: 10.1016/S0140-6736(20)30252-X
  5. Soriano JB, Murthy S, Marshall JC, et al.; WHO Clinical Case Definition Working Group on Post-COVID-19 Condition. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022;22(4):e102–e107. doi: 10.1016/S1473-3099(21)00703-9
  6. Batiha GE, Al-Kuraishy HM, Al-Gareeb AI, et al. Pathophysiology of Post-COVID syndromes: a new perspective. Virol J. 2022;19(1):158. doi: 10.1186/s12985-022-01891-2
  7. Raveendran AV, Misra A. Post COVID-19 syndrome (“Long COVID”) and diabetes: challenges in diagnosis and management. Diabetes Metab Syndr. 2021;15(5):102235. doi: 10.1016/j.dsx.2021.102235
  8. Davis HE, McCorkell L, Vogel JM, et al. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023;21(1):133–146. doi: 10.1038/s41579-022-00846-2 Erratum in: Nat Rev Microbiol. 2023;21(6):408. doi: 10.1038/s41579-023-00896-0
  9. Burks SM, Rosas-Hernandez H, Alejandro Ramirez-Lee M, et al. Can SARS-CoV-2 infect the central nervous system via the olfactory bulb or the blood-brain barrier? Brain Behav Immun. 2021;95:7–14. doi: 10.1016/j.bbi.2020.12.031
  10. Granholm AC. Long-term effects of SARS-CoV-2 in the brain: clinical consequences and molecular mechanisms. J Clin Med. 2023;12(9):3190. doi: 10.3390/jcm12093190
  11. Frank S. Catch me if you can: SARS-CoV-2 detection in brains of deceased patients with COVID-19. Lancet Neurol. 2020;19(11):883–884. doi: 10.1016/S1474-4422(20)30371-9
  12. Gafson AR, Barthelemy NR, Bomont P, et al. Neurofilaments: neurobiological foundations for biomarker applications. Brain. 2020;143(7):1975–1998. doi: 10.1093/brain/awaa098
  13. Zingaropoli MA, Pasculli P, Barbato C, et al. Biomarkers of neurological damage: From acute stage to post-acute sequelae of COVID-19. Cells. 2023;12(18):2270. doi: 10.3390/cells12182270
  14. Chaumont H, Kaczorowski F, San-Galli A, et al. Cerebrospinal fluid biomarkers in SARS-CoV-2 patients with acute neurological syndromes. Rev Neurol (Paris). 2022;179(3):208–217. doi: 10.1016/j.neurol.2022.11.002
  15. Jeong GU, Lyu J, Kim KD, et al. SARS-CoV-2 infection of microglia elicits proinflammatory activation and apoptotic cell death. Microbiol Spectr. 2022;29(3):e0109122. doi: 10.1128/spectrum.01091-22
  16. Theoharides TC, Kempuraj D. Role of SARS-CoV-2 spike-protein-induced activation of microglia and mast cells in the pathogenesis of neuro-COVID. Cells. 2023;12(5):688. doi: 10.3390/cells12050688
  17. Skaper SD, Facci L, Zusso M, et al. Neuroinflammation, mast cells, and glia: dangerous liaisons. Neuroscientist. 2017;23(5):478–498. doi: 10.1177/1073858416687249
  18. Appelman B, Charlton BT, Goulding RP, et al. Muscle abnormalities worsen after post-exertional malaise in long COVID. Nat Commun. 2024;15(1):17. doi: 10.1038/s41467-023-44432-3
  19. Raman B, Bluemke DA, Lüscher TF, Neubauer S. Long COVID: post-acute sequelae of COVID-19 with a cardiovascular focus. Eur Heart J. 2022;43(11):1157–1172. doi: 10.1093/eurheartj/ehac031
  20. Carlson FR, Bosukonda D, Keck PC, Carlson WD. Multiorgan damage in patients with COVID-19: Is the TGF-β/BMP pathway the missing link? JACC Basic Transl Sci. 2020;5(11):1145–1148. doi: 10.1016/j.jacbts.2020.09.003
  21. Puntmann VO, Carerj ML, Wieters I, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265–1273. doi: 10.1001/jamacardio.2020.3557 Erratum in: JAMA Cardiol. 2020;5(11):1308. doi: 10.1001/jamacardio.2020.4648
  22. Thompson BT, Chambers RC, Liu KD. Acute respiratory distress syndrome. N Engl J Med. 2017;377(6):562–572. doi: 10.1056/NEJMra1608077
  23. Schwensen HF, Borreschmidt LK, Storgaard M, et al. Fatal pulmonary fibrosis: a post-COVID-19 autopsy case. J Clin Pathol. 2021;74(6):400–402. doi: 10.1136/jclinpath-2020-206879
  24. Kouzbari K, Hossan MR, Arrizabalaga JH, et al. Oscillatory shear potentiates latent TGF-β1 activation more than steady shear as demonstrated by a novel force generator. Sci Rep. 2019;9(1):6065. doi: 10.1038/s41598-019-42302-x
  25. Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601–615. doi: 10.1038/s41591-021-01283-z
  26. Townsend L, Fogarty H, Dyer A, et al. Prolonged elevation of D-dimer levels in convalescent COVID-19 patients is independent of the acute phase response. J Thromb Haemost. 2021;19(4):1064–1070. doi: 10.1111/jth.15267
  27. Poloni TE, Moretti M, Medici V, et al. COVID-19 pathology in the lung, kidney, heart and brain: The different roles of T-cells, macrophages, and microthrombosis. Cells. 2022;11(19):3124. doi: 10.3390/cells11193124
  28. Fallahi P, Elia G, Ragusa F, et al. Thyroid autoimmunity and SARS-CoV-2 infection. J Clin Med. 2023;12(19):6365. doi: 10.3390/jcm12196365
  29. Lania A, Sandri MT, Cellini M, et al. Thyrotoxicosis in patients with COVID-19: The THYRCOV study. Eur J Endocrinol. 2020;183(4):381–387. doi: 10.1530/EJE-20-0335
  30. Brancatella A, Viola N, Santini F, Latrofa F. COVID-induced thyroid autoimmunity. Best Pract Res Clin Endocrinol Metab. 2023;37(2):101742. doi: 10.1016/j.beem.2023.101742
  31. Sathish T, Cao Y, Kapoor N. Newly diagnosed diabetes in COVID-19 patients. Prim Care Diabetes. 2021;15(1):194. doi: 10.1016/j.pcd.2020.08.014
  32. Müller JA, Groß R, Conzelmann C, et al. SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas. Nat Metab. 2021;3(2):149–165. doi: 10.1038/s42255-021-00347-1
  33. Pizzini A, Aichner M, Sahanic S, et al. Impact of vitamin D deficiency on COVID-19: A prospective analysis from the CovILD registry. Nutrients. 2020;12(9):2775. doi: 10.3390/nu12092775
  34. Sapra L, Saini C, Garg B, et al. Long-term implications of COVID-19 on bone health: Pathophysiology and therapeutics. Inflamm Res. 2022;71(9):1025–1040. doi: 10.1007/s00011-022-01616-9
  35. Chen Z, Hu J, Liu L, et al. SARS-CoV-2 causes acute kidney injury by directly infecting renal tubules. Front Cell Dev Biol. 2021;9:664868. doi: 10.3389/fcell.2021.664868
  36. Chang YC, Lee D-J, Wei C-L, et al. SARS-CoV-2 versus other minor viral infections on kidney injury in asymptomatic and mildly symptomatic patients. Virulence. 2022;13(1):1349–1357. doi: 10.1080/21505594.2022.2107602
  37. Benedetti C, Waldman M, Zaza G, et al. COVID-19 and the kidneys: an update. Front Med (Lausanne). 2020;7:423. doi: 10.3389/fmed.2020.00423
  38. Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2023;401(10393):e21–e33. doi: 10.1016/S0140-6736(23)00810-3
  39. Castanares-Zapatero D, Chalon P, Kohn L, et al. Pathophysiology and mechanism of long COVID: A comprehensive review. Ann Med. 2022;54(1):1473–1487. doi: 10.1080/07853890.2022.2076901
  40. Panigrahy D, Gilligan MM, Serhan CN, Kashfi K. Resolution of inflammation: An organizing principle in biology and medicine. Pharmacol Ther. 2021;227:107879. doi: 10.1016/j.pharmthera.2021.107879
  41. Oronsky B, Larson C, Hammond TC, et al. A review of persistent post-COVID syndrome (PPCS). Clin Rev Allergy Immunol. 2023;64(1):66–74. doi: 10.1007/s12016-021-08848-3
  42. Peluso MJ, Deitchman AN, Torres L, et al. Long-term SARS-CoV-2-specific immune and inflammatory responses in individuals recovering from COVID-19 with and without post-acute symptoms. Cell Rep. 2021;36(6):109518. doi: 10.1016/j.celrep.2021.109518
  43. Ramakrishnan RK, Kashour T, Hamid Q, et al. Unraveling the mystery surrounding post-acute sequelae of COVID-19. Front Immunol. 2021;12:2574. doi: 10.3389/fimmu.2021.686029
  44. Swank Z, Senussi Y, Manickas-Hill Z, et al. Persistent circulating SARS-CoV-2 spike is associated with post-acute coronavirus disease 2019 sequelae. Clin Infect Dis. 2023;76(3):e487–e490. doi: 10.1093/cid/ciac722
  45. Stein SR, Ramelli SC, Grazioli A, et al. SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature. 2022;612(7941):758–763. doi: 10.1038/s41586-022-05542-y
  46. Natarajan A, Zlitni S, Brooks EF, et al. Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection. Med. 2022;3(6):371–387.e9. doi: 10.1016/j.medj.2022.04.001
  47. Ryan PMD, Caplice NM. Is adipose tissue a reservoir for viral spread, immune activation, and cytokine amplification in coronavirus disease? Obesity (Silver Spring). 2020;28(7):1191–1194. doi: 10.1002/oby.22843
  48. Opsteen S, Files JK, Fram T, et al. The role of immune activation and antigen persistence in acute and long COVID. J Invest Med. 2023;71(5):545–562. doi: 10.1177/10815589231158041
  49. Galán M, Vigón L, Fuertes D, et al. Persistent overactive cytotoxic immune response in a Spanish cohort of individuals with long-COVID: identification of diagnostic biomarkers. Front Immunol. 2022;13:848886. doi: 10.3389/fimmu.2022.848886
  50. Phetsouphanh C, Darley DR, Wilson DB, et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol. 2022;23(2):210–216. doi: 10.1038/s41590-021-01113-x
  51. Queiroz MAF, Neves PFM, Lima SS, et al. Cytokine profiles associated with acute COVID-19 and long COVID-19 syndrome. Front Cell Infect Microbiol. 2022;12:922422. doi: 10.3389/fcimb.2022.922422
  52. Schultheiss C, Willscher E, Paschold L, et al. The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19. Cell Rep Med. 2022;3(6):100663. doi: 10.1016/j.xcrm.2022.100663
  53. Wechsler JB, Butuci M, Wong A, et al. Mast cell activation is associated with post-acute COVID-19 syndrome. Allergy. 2022;77(4):1288–1291. doi: 10.1111/all.15188
  54. Pisareva E, Badiou S, Mihalovičová L, et al. Persistence of neutrophil extracellular traps and anticardiolipin auto-antibodies in post-acute phase COVID-19 patients. J Med Virol. 2023;95(1):e28209. doi: 10.1002/jmv.28209
  55. Son K, Jamil R, Chowdhury A, et al. Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long COVID symptoms. Eur Respir J. 2023;61(1):2200970. doi: 10.1183/13993003.00970-2022
  56. Kanduc D. From anti-SARS-CoV-2 immune responses to COVID-19 via molecular mimicry. Antibodies (Basel). 2020;9(3):33. doi: 10.3390/antib9030033
  57. Lerner A, Benzvi C, Vojdani A. SARS-CoV-2 gut-targeted epitopes: sequence similarity and cross-reactivity join together for molecular mimicry. Biomedicines. 2023;11(7):1937. doi: 10.3390/biomedicines11071937
  58. Richter AG, Shields AM, Karim A, et al. Establishing the prevalence of common tissue-specific autoantibodies following severe acute respiratory syndrome coronavirus 2 infection. Clin Exp Immunol. 2021;205(2):99–105. doi: 10.1111/cei.13623
  59. Wallukat G, Hohberger B, Wenzel K, et al. Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms. J Transl Autoimmun. 2021;4:100100. doi: 10.1016/j.jtauto.2021.100100
  60. Schofield JR. Persistent antiphospholipid antibodies, mast cell activation syndrome, postural orthostatic tachycardia syndrome and post-COVID syndrome: 1 year on. Eur J Case Rep Intern Med. 2021;8(3):002378. doi: 10.12890/2021_002378
  61. Tang SW, Helmeste D, Leonard B. Inflammatory neuropsychiatric disorders and COVID-19 neuroinflammation. Acta Neuropsychiatr. 2021;33(4):165–177. doi: 10.1017/neu.2021.13
  62. Bastard P, Rosen LB, Zhang Q, et al. Autoantibodies against type I interferons in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4585. doi: 10.1126/science.abd4585
  63. Wang X, Tang Q, Li H, et al. Autoantibodies against type I interferons in COVID-19 infection: A systematic review and meta-analysis. Int J Infect Dis. 2023;130:147–152. doi: 10.1016/j.ijid.2023.03.011
  64. Koning R, Bastard P, Casanova JL. Autoantibodies against type I interferons are associated with multi-organ failure in COVID-19 patients. Intensive Care Med. 2021;47(6):704–706. doi: 10.1007/s00134-021-06392-4

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© Klimov N.A., Simbirtsev A.S., 2025